A patient's obesity may negatively affect a common drug that is used as part of the treatment to fight breast cancer in post-menopausal women.

This is according to Professor Mark Elwood, an Auckland University expert in cancer epidemiology, who has authored a review on the effect of obesity of aromatase inhibitors (AIs), which are used to treat cancer.

Considered the best hormonal therapy to start with when treating early-stage, hormone-receptor-positive breast cancer, aromatase inhibitor pills are usually taken once a day.

AIs less effective

Aromatase inhibitors stop the production of oestrogen in post-menopausal women by blocking the enzyme aromatase, which turns the hormone androgen into small amounts of oestrogen in the body. This means that less oestrogen is available to stimulate the growth of hormone-receptor-positive breast cancer cells.

“AIs may be less effective in obese women due to the greater quantity of aromatase in peripheral fatty tissue,” said Prof. Elwood.

The author looked at eight earlier interventional or observational studies with comparison groups of post-menopausal women with hormone-receptor-positive breast cancer on treatment with an AI—either alone or in combination with other drugs in which body mass index or another measure of obesity was used.

“Outcome measures included overall survival, disease-free survival or time to progressive disease, survival from the start of therapy, mortality measures, local or distant recurrence of primary cancer and time to recurrence,” said medical oncologist Dr David Porter, the report's co-author.

“The systematic review showed a trend towards a negative effect of obesity on AI efficacy, but the size of the effect [in post-menopausal hormone-receptor-positive breast cancer], and whether it is the same with all AIs is difficult to determine.”

Questions unanswered

However, more information is needed before clinical recommendations are made, Dr Porter said.

“AIs are prescribed at a fixed dose in all patients, but the apparent decreased efficacy in heavier patients warrants investigation of whether higher doses would be more effective in obese women.

“It is important for physicians to contemplate more individualised treatment choices to limit the number of non-responders to treatment and to improve the likelihood of successful therapy for all patients.”

Prof. Elwood added: “Many questions remain unanswered in this complex scenario and information is needed before recommendations for the improved use of AIs for obese patients could or should be made.

“Further evidence on the differing potencies of the major AIs in obesity would help clarify whether specific AIs may yield a better outcome in obese patients or whether prescribing higher doses of AIs might be useful.”

Now defined as a global pandemic, obesity is predicted to affect more than half of the world’s population by 2030. The condition is already associated with an increased risk of several cancers and poorer outcomes for cancers such as colon, endometrial and post-menopausal breast cancer.

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